Tumor Biology

, Volume 37, Issue 5, pp 6177–6184 | Cite as

Epithelial–mesenchymal transition plays a critical role in drug resistance of hepatocellular carcinoma cells to oxaliplatin

  • Jun li Ma
  • Shan Zeng
  • Yan Zhang
  • Gan lu Deng
  • Hong Shen
Original Article

Abstract

Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial–mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.

Keywords

Hepatocellular carcinoma Oxaliplatin Drug resistance Epithelial–mesenchymal transition 

Notes

Acknowledgments

This study was supported by the grants from the National Nature Science Foundation of China (No. 30770971, 81172470, 81070362, and 81372629).

Compliance with ethical standards

The manuscript has been performed with the approval of the institutional Ethics Committees of Xiangya Hospital, Central South University.

Conflicts of interest

The authors declare that they have no competing interests.

Supplementary material

13277_2015_4458_MOESM1_ESM.doc (46 kb)
Supplementary Table S1 The types, dilutions and sources of antibodies used for the Western blot analysis. (DOC 46 kb)
13277_2015_4458_Fig7_ESM.gif (11 kb)
Figure S1

Downregulation of Snail expression by siRNAs in Bel-7402/OXA cells. Western blot (a) and qRT-PCR (b) demonstrated that siRNA 2 had the highest inhibition efficiency of 71.7% in the three candidate sequences. (GIF 10 kb)

13277_2015_4458_MOESM2_ESM.tif (125 kb)
High resolution image (TIF 124 kb)
13277_2015_4458_Fig8_ESM.gif (30 kb)
Figure S2

Regulation of EMT transcription factors effected OXA resistance. a Cell viability of Bel-7402/OXA after Slug knockdown was measured by CCK-8 assay (p < 0.001). b Cell viability of Bel-7402/OXA after Twist knockdown was measured by CCK-8 assay (p < 0.05). (GIF 29 kb)

13277_2015_4458_MOESM3_ESM.tif (2.7 mb)
High resolution image (TIF 2813 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jun li Ma
    • 1
  • Shan Zeng
    • 1
  • Yan Zhang
    • 1
  • Gan lu Deng
    • 1
  • Hong Shen
    • 1
  1. 1.Department of Oncology, Xiangya HospitalCentral South UniversityChangshaChina

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